BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.
BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLCpatients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLCpatients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.
Authors: F Koinis; A Voutsina; A Kalikaki; A Koutsopoulos; E Lagoudaki; E Tsakalaki; E K Dermitzaki; E Kontopodis; A G Pallis; V Georgoulias; A Kotsakis Journal: Clin Transl Oncol Date: 2017-06-19 Impact factor: 3.405
Authors: William D Travis; Elisabeth Brambilla; Masayuki Noguchi; Andrew G Nicholson; Kim Geisinger; Yasushi Yatabe; Yuichi Ishikawa; Ignacio Wistuba; Douglas B Flieder; Wilbur Franklin; Adi Gazdar; Philip S Hasleton; Douglas W Henderson; Keith M Kerr; Iver Petersen; Victor Roggli; Erik Thunnissen; Ming Tsao Journal: Arch Pathol Lab Med Date: 2012-09-12 Impact factor: 5.534
Authors: Coren A Milbury; Clark C Chen; Harvey Mamon; Pingfang Liu; Sandro Santagata; G Mike Makrigiorgos Journal: J Mol Diagn Date: 2011-03 Impact factor: 5.568
Authors: William D Travis; Elisabeth Brambilla; Masayuki Noguchi; Andrew G Nicholson; Kim R Geisinger; Yasushi Yatabe; David G Beer; Charles A Powell; Gregory J Riely; Paul E Van Schil; Kavita Garg; John H M Austin; Hisao Asamura; Valerie W Rusch; Fred R Hirsch; Giorgio Scagliotti; Tetsuya Mitsudomi; Rudolf M Huber; Yuichi Ishikawa; James Jett; Montserrat Sanchez-Cespedes; Jean-Paul Sculier; Takashi Takahashi; Masahiro Tsuboi; Johan Vansteenkiste; Ignacio Wistuba; Pan-Chyr Yang; Denise Aberle; Christian Brambilla; Douglas Flieder; Wilbur Franklin; Adi Gazdar; Michael Gould; Philip Hasleton; Douglas Henderson; Bruce Johnson; David Johnson; Keith Kerr; Keiko Kuriyama; Jin Soo Lee; Vincent A Miller; Iver Petersen; Victor Roggli; Rafael Rosell; Nagahiro Saijo; Erik Thunnissen; Ming Tsao; David Yankelewitz Journal: J Thorac Oncol Date: 2011-02 Impact factor: 15.609
Authors: Ronald van Eijk; Marjo van Puijenbroek; Amiet R Chhatta; Nisha Gupta; Rolf H A M Vossen; Esther H Lips; Anne-Marie Cleton-Jansen; Hans Morreau; Tom van Wezel Journal: J Mol Diagn Date: 2009-12-03 Impact factor: 5.568